This revised application for competing continuation of an Independent Scientist Award (K02) entitled "Monoarninergic Function in Geriatric Neuropsychiatry" outlines a career development plan to further enhance the candidate's research and the scope of her mentorship activities as she has done over the past five years. The candidate's research career has focused on the development and application of methods that has integrated Positron Emission Tomography (PET) imaging of glucose metabolism and neuroreceptors with pharmacologic interventions to evaluate monoaminergic function in vivo. The candidate has conducted her research and training activities by collaborating with senior investigators in interventions and neurobiologic research in schizophrenia, Alzheimer's disease (AD) and geriatric depression. These collaborations have enabled her to pursue the overarching theme of her funded research that decreased monoaminergic responsiveness is related to pathophysiology and thus, to the response to pharmacotherapy across these disorders. She has accomplished the primary goal of the initial award period of integrating neurochemical brain imaging studies into clinical trials. The primary research focus of the past five years was the development and application of in vivo methods to evaluate serotonergic function and modulation by other neurotransmitters (dopamine, acetylcholine) in neuropsychiatric disorders. The research and training activities conducted in the next five years will focus on 1) the completion of several funded projects to evaluate serotonin function in schizophrenia, Alzheimer's Disease and geriatric depression, 2) the initiation of mechanistic and intervention studies in these disorders that focus on further elucidating serotonin and dopamine function and 3) training in the areas of neuropharmacology, preclinical, postmortem and in vivo imaging of monoaminergic systems. The long-term goal of the candidate's research is to understand the pathophysiology of treatment response variability in neuropsychiatric disorders of the elderly by developing and applying neuropharmacologic imaging methods. The Independent Scientist Award will enable the candidate to continue to firmly focus her research and mentorship activities in the area of geriatric neuropsychiatry.